Dataset Information

Biological role and clinical value of miR-99a-5p in head and neck squamous cell carcinoma (HNSCC): A bioinformatics-based study.

ABSTRACT: MicroRNAs (miRNAs) are confirmed to be tumor promoters or suppressors in multiple squamous cell carcinomas (SCCs). miR-99a-5p has been demonstrated to be downregulated in cancerous tissues, but its functional role in head and neck SCC (HNSCC) and its mechanism of action have not been fully elucidated. Here, we studied the expression of miR-99a-5p in HNSCC and performed a clinical value assessment and then extracted mature expression data from The Cancer Genome Atlas (TCGA) and microarrays from Gene Expression Omnibus (GEO). Furthermore, biological analysis was constructed via online prediction tools. The results revealed that miR-99a-5p expression was markedly lower in HNSCC tissues than in normal tissues, which also showed significance in the prognosis of HNSCC. However, its diagnostic value could not be verified due to the lack of body fluid samples. Additionally, miR-99a-5p was expressed at higher levels in patients with low histological grade neoplasms than those with high histological grade neoplasms. The age of the patient might also be a possible clinical parameter affecting miR-99a-5p expression. Furthermore, miR-99a-5p significantly influenced HNSCC progression by regulating the PI3K-Akt signaling pathway, in which the key target genes were upregulated in 519 HNSCC tissues compared to 44 normal tissues, as determined by the Gene Expression Profiling Interactive Analysis (GEPIA). In conclusion, our study may provide insights into the expression and mechanism of miR-99a-5p in HNSCC. Further studies are required to elucidate the role of miR-99a-5p and its potential clinical applications for HNSCC.

SUBMITTER: Chen YT

PROVIDER: S-EPMC6070648 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Biological role and clinical value of miR-99a-5p in head and neck squamous cell carcinoma (HNSCC): A bioinformatics-based study.

Chen Yu-Ting YT Yao Jian-Ni JN Qin Yu-Tao YT Hu Kai K Wu Fang F Fang Ye-Ying YY

FEBS open bio 20180626 8

MicroRNAs (miRNAs) are confirmed to be tumor promoters or suppressors in multiple squamous cell carcinomas (SCCs). miR-99a-5p has been demonstrated to be downregulated in cancerous tissues, but its functional role in head and neck SCC (HNSCC) and its mechanism of action have not been fully elucidated. Here, we studied the expression of miR-99a-5p in HNSCC and performed a clinical value assessment and then extracted mature expression data from The Cancer Genome Atlas (TCGA) and microarrays from G ...[more]

PMID: 30087832

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Project description:Aim: Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed malignancy worldwide. Overexpressed of microRNA-21-5p (miR-21-5p) has been reported to be involved in the development of HNSCC. However, the role of miR-21-5p in HNSCC is still not fully elucidated. The purpose of this study was to explore the underlying molecular mechanisms of miR-21-5p in HNSCC. Methods: RT-qPCR was used to determine the differential expression levels of miR-21-5p in tissue samples of HNSCC patients. Meta-analysis was performed based on miRNA expression data collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA), and published articles to evaluate the expression of miR-21-5p in HNSCC. We investigated the biological function of miR-21-5P by gene ontology enrichment and target prediction analysis. Furthermore, RT-qPCR and IHC were conducted to verify the expression of target genes. Finally, Kaplan-Meier survival analysis was performed to assessed the prognostic value of the putative miR-21-5p target genes. Results: MiR-21-5p was significantly overexpressed in HNSCC compared to healthy tissues (P < .05) and showed potent predictive power with a summary receiver operating characteristic of 0.90. Meanwhile, the expression of miR-21-5p was significantly correlated with tumor stage, T stage and smoking in HNSCC (P < .05). A total of 71 down-regulated genes, both HNSCC-related and miR-21-p5-related, were obtained from the analytical integration. Two predicted genes (ADH7, RDH12) were down-regulated in HNSCC, and significantly negatively correlated with miR-21-5p. IHC and RT-qPCR demonstrated that the expression of ADH7 and RDH12 in HNSCC samples was significantly lower than control. And high expression of ADH7 was associated with better DFS of HNSCC patients. Conclusions: miR-21-5p may target at ADH7, RDH12 and participate in regulation of retinol metabolism, which might affect the prognosis of HNSCC. High expression of ADH7 may indicate better prognosis in HNSCC patients.

Project description:This study demonstrated that miR‐335‐5p expression was reduced in HNSCC. miR‐335‐5p expression could inhibit HNSCC cell growth, metastasis, and promote cell apoptosis while it could suppress tumor growth in vivo. We identified MAP3K2 as a novel target of miR‐335‐5p and MAP3K2 overexpression partially rescued the inhibitory role of miR‐335‐5p. Hence, miR‐335‐5p might constitute a potential therapeutic target for HNSCC patients. Mounting evidence has indicated that aberrantly expressed microRNAs (miRNAs) play key roles in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). Previous studies have shown that miR‐335‐5p can serve as a tumor suppressor or an oncogene in cancer. However, the clinical importance and biological effects of miR‐335‐5p in HNSCC have not been determined. Here, we investigated the expression pattern, functional role, and mechanisms of miR‐335‐5p in HNSCC. We showed a decreased expression of miR‐335‐5p in HNSCC samples from the TCGA and GEO databases. Consistently, we detected a downregulation of miR‐335‐5p in HNSCC cell lines and patient tissues. The expression of miR‐335‐5p was inversely correlated with advanced clinical TNM stage and lymph node metastasis in HNSCC patients. miR‐335‐5p overexpression inhibited HNSCC cell proliferation and induced apoptosis, while miR‐335‐5p inhibition had the opposite effects. miR‐335‐5p overexpression suppressed tumor growth in mice. Bioinformatic analyses and functional assays identified MAP3K2 as a target of miR‐335‐5p, and we showed that miR‐335‐5p downregulated mitogen‐activated protein kinase kinase kinase 2 (MAP3K2) expression in HNSCC cells. We found an inverse association between MAP3K2 and miR‐335‐5p expression in 38 pairs of HNSCC tissues. Furthermore, the effect of miR‐335‐5p overexpression on growth and metastasis as well as cell apoptosis in HNSCC cells could be partially rescued by MAP3K2 expression. Collectively, our data show that miR‐335‐5p inhibits the development of HNSCC by regulating MAP3K2 expression. Thus, these findings offer novel insights into a potential therapeutic strategy for HNSCC patients.

Project description:BackgroundLocal or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients. MicroRNAs (miRNAs) have been implicated in metastasis of HNSCC, but the mechanisms of their action are mainly undocumented. Through public head and neck cancer miRNA expression datasets, we found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC metastasis.MethodsClinical significance and mechanism of miR-876-5P was systematically analyzed in HNSCC. Quantitative RT-PCR was used to evaluate miR-876-5p levels in HNSCC cell lines and in 20 pairs of HNSCC with associated regional nodal metastases and HNSCC without metastatic primary tumors. Scratch and invasion assays were evaluated to determine the role of miR-876-5p in the regulation of HNSCC cell migration and invasion, respectively. Western blotting was used to investigate the mechanism by which miR-876-5p suppresses HNSCC cell invasion and migration. Luciferase assays were performed to assess miR-876-5p binding to the vimentin gene. The animal model was used to support the in vitro experimental findings.ResultsMiR-876-5p mimics inhibited HNSCC cell migration and invasion. Vimentin protein and mRNA levels were decreased in the miR-876-5p mimics group but increased in the miR-876-5p inhibitors group, which demonstrated that miR-876-5p inhibits vimentin expression in HNSCC cells. By directly targeting the vimentin 3'-UTR, we used dual-luciferase reporter assays to verify that vimentin is a functional downstream target of miR-876-5p. Importantly, increased vimentin expression promoted cell migration and invasion, and co-transfection with miR-876-5p mimics and vimentin restored cell aggressiveness to the original level. Moreover, miR-876-5p overexpression significantly downregulated vimentin expression level and inhibited the distal metastasis of HNSCC cells in vivo.ConclusionsmiR-876-5p, which functions as a tumor suppressor in HNSCC, inhibits metastasis by targeting vimentin and provides a novel therapeutic target for HNSCC treatment.

Dataset Information

Biological role and clinical value of miR-99a-5p in head and neck squamous cell carcinoma (HNSCC): A bioinformatics-based study.

Publications

Biological role and clinical value of miR-99a-5p in head and neck squamous cell carcinoma (HNSCC): A bioinformatics-based study.

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